Barrett's esophagus is a condition in which the lower esophagus is lined with metaplastic columnar epithelium rather than the normal stratified squamous epithelium. It is associated with an increased risk of cancer. Cancers arising from Barrett's epithelium are adenocarcinomas rather than the usual squamous cell esophageal cancers. Barrett's is somewhat unique amongst premalignant lesions, since it represents an entirely different epithelium from the normal and, therefore, can be histologically identified with certainty. Consequently, it offers an unusual opportunity to study and characterize premalignant lesions for adenocarcinomas. At our institution we have over 70 patients with histologically confirmed Barrett's esophagus that are part of a clinical study to prospectively define the natural history of the disease. New patients are being entered at a rate of approximately 2 per month. This provides an invaluable resource for combined laboratory and clinical investigations. Specific aims of the present proposal are to: (1) establish and characterize cell lines from Barrett's epithelium; (2) use the cell lines to study the effect of drugs and biologic response modifiers on growth and differentiation of Barrett's epithelial cells; and (3) extend our preliminary observations on elevated ornithine decarboxylase (ODC) levels in Barrett's mucosa and test the effect of ODC inhibitors on cultured Barrett's cells. The long-term goal of this study is to develop an in vitro model of a premalignant lesion for adenocarcinoma using Barrett's mucosal epithelium. Availability of such a model would clearly be of utility to investigators in the field of carcinogenesis, cancer etiology and prevention. The equally important, but shorter term objective, is to find successful medical therapy for treating Barrett's esophagus. From a clinical standpoint, any agents that are found to be active in Barrett's esophagus may prove to be useful in other premalignant lesions of adenocarcinomas.